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Aim: The aim of our study was to assess glial fibrillary acidic protein (GFAP) glial cell phenotype in the enteric nervous system (ENS) in colorectal adenocarcinoma of different tumor grading and, also, to establish correlations between these changes and the tumor proliferative activity and the tumor-infiltrating leukocytes., Patients, Materials and Methods: We ran an observational, prospective study on a group of 52 patients diagnosed with colorectal adenocarcinoma. They were surgically treated in the 1st Surgery Clinic of the Emergency County Hospital of Craiova, Romania. From the surgically resected pieces, after pathological confirmation and tumor grading, 3-μm thick seriate sections were cut and processed for immunohistochemistry for detecting GFAP, S100, CD45 and Ki-67., Results: Evaluation of GFAP glial cell type in the ENS of colorectal cancer with different stages of differentiation showed that the density of these nervous elements is higher in well-differentiated (G1) colorectal tumors compared to moderately differentiated (G2) and poorly differentiated (G3) colorectal tumors. For well-differentiated colorectal adenocarcinoma, we did not find any correlations between GFAP glial cell type in the ENS and the tumor proliferative activity or with tumor-infiltrating leukocytes. In what the moderately and poorly differentiated adenocarcinoma are concerned, we found a high inverse variation between GFAP glial cell type in the ENS and the proliferative activity, on one hand, and, between GFAP glial cell type in the ENS and the tumor-infiltrating leukocytes, on the other hand., Conclusions: The decrease in the density of GFAP glial cell type in the ENS with tumor grading of colorectal cancer and the inverse variation with the tumor proliferative activity and with the tumor-infiltrating leukocytes might serve as putative prognostic factors in colorectal cancer.